Catalytic C2 prenylation of unprotected indoles: Late-stage diversification of peptides and two-step total synthesis of tryprostatin B

C2 prenylated indoles are widespread in a variety of bioactive natural alkaloids. Therefore, the selective installation of prenyl group at C2 position of NH indoles is of great significance. However, the known protocols generally require a multi-step procedure and stoichiometric promoters. Herein we develop a one-step C2 prenylation of NH indole with cheap tert-prenyl alcohol enabled by acid catalysis. Salient features include good regioselectivity, step- and atom-economy, broad substrate scope, and simple catalytic system. The mechanistic investigations demonstrate that both C2 prenylation and C3 prenylation/migration pathways are engaged in the reaction. Notably, this practical strategy can be applied to the late-stage diversification of tryptophan-based peptides and concise synthesis of tryprostatin B. (C) 2021, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Automated summary

The study presents a straightforward method for C2 prenylation of NH indoles with good regioselectivity and broad substrate scope. The one-step process, catalyzed by acid, is efficient and atom-economical, suitable for late-stage diversification of tryptophan-based peptides and concise synthesis of tryprostatin B.